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The influence of CYP2C9 and VKORC1 gene polymorphisms on optimal warfarin doses after heart valve replacement

Vacis Tatarūnas1, Vaiva Lesauskaitė, Audronė Veikutienė

  • 1Institute of Cardiology, Me-dical Academy, Lithuanian University of Health Sciences, Suki-lėlių 17, 50161 Kaunas, Lithuania. vacis_tatarunas@takas.lt

Medicina (Kaunas, Lithuania)
|June 18, 2011
PubMed
Abstract

Insights

Warfarin dosage in Lithuanian heart surgery patients is influenced by CYP2C9 and VKORC1 gene variants. Understanding these genetic factors helps personalize warfarin treatment for better outcomes.

Area of Science:

  • Pharmacogenomics
  • Clinical Biochemistry
  • Cardiovascular Surgery

Background:

  • Warfarin's clinical effect is influenced by genetic variations in drug-metabolizing enzymes like CYP2C9 and drug-target enzymes like VKORC1.
  • Understanding these genetic polymorphisms is crucial for optimizing warfarin therapy, especially in post-operative patients.

Purpose of the Study:

  • To investigate the impact of CYP2C9*2, CYP2C9*3, and VKORC1 (G-1639A) polymorphisms on warfarin dosage variability.
  • To analyze genetic influences on warfarin requirements in Lithuanian patients following heart valve replacement.

Main Methods:

  • Study included 83 patients undergoing heart valve replacement with stable international normalized ratio (INR) levels.
  • Restriction fragment length polymorphism (RFLP) method was employed to identify VKORC1 and CYP2C9 gene polymorphisms.

Main Results:

  • Daily warfarin dosage correlated significantly with patient weight and height.
  • Wild-type CYP2C9*1/*1 genotype was linked to higher warfarin doses compared to other genotypes.
  • Carriers of VKORC1 (G/G) genotype required higher warfarin doses than (A/A) carriers (P=0.04).
  • Combined CYP2C9 and VKORC1 genotypes influenced the highest daily warfarin dosage requirements.

Conclusions:

  • The Lithuanian population exhibits a high frequency (92.8%) of VKORC1 G/G and G/A genotypes, necessitating higher warfarin loading doses.
  • Analyzing combined CYP2C9 and VKORC1 gene variants can predict warfarin dosage requirements.
  • These findings support the individualization of warfarin treatment in Lithuanian cardiac surgery patients.

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